Schizophrenia is a psychological disorder showing diverse symptoms such as delusion, hallucination, hyperactivity, and depression. These symptoms are broadly classified as positive symptoms, negative symptoms, and cognitive disorders, Hitherto, in the treatment of schizophrenia, D2 receptor blockers such as haloperidol which is a typical first generation antipsychotic drug and Risperidone, Olanzapine, and the like, which are atypical second generation antipsychotic drugs have been discovered, and have exhibited some effects in the treatment of positive symptoms. However, side effects have been reported such as extrapyramidal symptoms with the first generation haloperidol or the like and metabolic disorders, for example, obesity, hyperglycemia, and the like with the second generation Risperidone, Olanzapine, and the like (Am. J. Psychiatry, 2003, 160: 1209-1222; Neuropsychopharmacology, 2003. 28: 1400-11; Diabetes Care, 2004, 27: 596; Japanese Journal of Clinical Psychopharmacology 2005, 8: 2151-64; Mol. Psychiatry. 2008, 13: 27-35). In addition, with conventional type drugs, the drug efficacy is insufficient with respect to negative symptoms or cognitive disorders (Schizophrenia Res, 2006, 88: 5-25; Japanese Journal of Clinical Psychopharmacology 2005, 8: 2151-64). In particular, in recent years, it has become common knowledge that cognitive disorders in schizophrenia are universally present, and while it has become clear that these disorders are greatly related to the prognosis, they are symptoms for which there is no effective therapeutic agent and for which there are medical unmet needs (Neuropsychology 1998, 12, 426-45; Am. J. Psychiatry 1996, 153: 321-30; Schizophrenia Bulletin 2000, 26: 119-36).
Dementia is a syndrome in which brain function is deteriorated by acquired brain disorders, and which is based on memory disorders and judgment disorders, and vascular dementia and Alzheimer's disease (below abbreviated to AD) are representative primary diseases. Hitherto, these therapeutic agents have been researched; however, the clinical satisfaction level is not sufficient. For example, with cholinesterase inhibitors such as donepezil which are widely used as therapeutic agents for AD, it has been reported that the effect is not sufficient (Curr. Neurol. Neurosci. rep., 2005, 5(6): 455-457; Eur. J. Pharmacol., 1998, 346: 1-13). Further, side effects due to stimulating the peripheral cholinergic nervous system have been noted (Cuff. Psychiatry Rep., 2000, 2(6): 473-478; J. Psychopharmacol., 2000, 14(4): 406-408). Further, NMDA antagonists such as memantine have been approved in some countries; however, side effects have been particularly noted in patients having psychological disorders such as cognitive disorders, hallucinations, ataxia, and mental diseases (J. Clin. Psychiatry. 2005, 66(5): 658-659; Learning & memory, 2001, 8: 20-25).
Against the above background, there is a demand for safe and highly effective therapeutic agents for schizophrenia and therapeutic agents for dementia.
It is known that cAMP-specific phosphodiesterase-4 (PDE4) is an enzyme related to second messenger cAMP regulation and deeply related to learning and memory functions (Science 1993, 260: 1661-4). It has been shown that PDE4 inhibitors promote neuronal plasticity in vitro, and improve or promote learning and memory in various models in vivo (PNAS 1998, 95: 15020-5; Current Pharmaceutical Design 2005, 11: 3329-34). Further, cAMP synthetic enzyme activity is decreased in AD patients and decrease in cAMP signal transduction in a pathological condition can be assumed (Neurobiol Aging 1997, 18: 275-9). Furthermore, some medical effects have been observed when treating human dementia patients with denbufylline, which is a PDE4 inhibitor (Biol Psychiatry 1992, 32: 668-81). However, vomiting is known as a common side effect of PDE4 inhibitors and this is an obstacle to development. In this regard, based on studies of brain expression and genetically modified mice, the possibility that the vomiting is mainly related to PDE4D has been suggested (Current Pharmaceutical design 2009, 15, 1693).
In addition, the relationship between PDE4B and schizophrenia has steadily become clearer in recent years. DISC1 (disrupted-in-schizophrenia 1) is a susceptible gene to schizophrenia and it has been shown that there is an interaction between PDE4B and DISC1, indicating that PDE4B is an important drug target (Current opinion Neurobiol 2007, 17: 95-102). In patients with schizophrenia, deterioration of the cAMP/PICA signal cascade function due to reduction in the brain PDE4B expression has been suggested (Schizophrenia Res 2008, 101: 36-49, 2008; J Neurochem 2002, 81: 745-57), indicating that PDE4B inhibitors are highly potential therapeutic agents for schizophrenia.
In addition, the fact that the classic PDE4 inhibitor rolipram has strong antidepressant effects has been confirmed in clinical trials; however, launching thereof has not been achieved due to the vomiting side effect (Current Therapeutic Res 1988, 43: 291-5). In recent years, since a relationship between PDE4B and depression is suggested (Psychopharmacol 2008, 197: 115-26) from analysis of PDE4B knockout mice, it is expected that there is a possibility that the PDE4B inhibitors will be able to avoid the vomiting side effect while having potent antidepressant effects.
Therefore, it can be believed that drugs inhibiting PDE4B are effective in the treatment or prevention of schizophrenia, Alzheimer's disease, dementia, depression, and the like.
In the chemical library of non-patent document 1, a structural formula of the compound represented by formula (A) is disclosed; however, there is no description of the PDE4 (PDE4B) inhibitory activity or of medicinal use with respect to schizophrenia, Alzheimer's disease, dementia, depression and the like.

In the chemical library of non-patent document 2, a structural formula of the compound represented by formula (B) is disclosed; however, there is no description of the PDE4 (PDE4B) inhibitory activity or of medicinal use with respect to schizophrenia, Alzheimer's disease, dementia, depression and the like.

In patent document 1, as one of the examples having various structures, it is reported that the compound represented by formula (C) in example 25 inhibits PDE4 and is useful in the treatment of inflammatory disease; however, there is no description of effectiveness for schizophrenia, Alzheimer's disease, dementia, depression and the like.

In patent document 2, as one of the examples having various structures, it is reported that the compound represented by formula (D) in example AAE has a microbial transcription factor regulation ability; however, there is no mention relating to PDE4 (PDE4B) inhibitory activity or description of effectiveness for schizophrenia, Alzheimer's disease, dementia, depression and the like.

In patent document 3, it is reported that compound represented by formula (E) is effective as an antifungal agent; however, there is no mention relating to PDE4 (PDE4B) inhibitory activity or description of effectiveness for schizophrenia, Alzheimer's disease, dementia, depression and the like,
(In the formula, A moiety is a benzene ring or the like, R1 is a monocyclic, bicyclic, or spirocyclic heterocyclic ring or the like of from 3 to 10 carbon atoms, R2 is an alkyl group or the like, or R1 and R2 may be put together and form a heterocyclic group of a 5-membered ring or 6-membered ring, R3 is an alkyl group or the like, and R4 is a cyano group,
or the like.For other details, refer to the Gazette.)
In patent document 3, as specific examples of the compound represented by (E), for example, the compound and the like of formula (F) are disclosed.

In non-patent document 3, a synthesis method of the compounds shown by formula (G) and formula (H) is disclosed; however, there is no mention relating to PDE4 (PDE4B) inhibitory activity or description of effectiveness for schizophrenia, Alzheimer's disease, dementia, depression and the like,
